尼古丁对载脂蛋白E^(-/-)小鼠调节性T细胞的影响

Effect of nicotine on regulatory T cells in ApoE^(-/-)mice

目的探讨不同浓度尼古丁刺激下,动脉粥样硬化斑块形成的变化及对外周血调节性T细胞的影响。方法 8周龄雄性载脂蛋白E(ApoE)基因敲除C57BL6J小鼠共18只,随机分为空白对照组(腹膜下注射生理盐水0.1mL/d)、低尼古丁组[腹膜下注射生理盐水稀释的尼古丁0.5mg/(kg·d)0.1mL]、高尼古丁组[腹膜下注射生理盐水稀释的尼古丁2.0mg/(kg·d)0.1mL],每组6只,用流式细胞仪检测外周血调节性T细胞改变及对ApoE-/-小鼠的主动脉根部行病理切片及HE染色。结果 12周后,与空白对照组比较,低、高尼古丁组粥样斑块面积增大[(0.304±0.055)、(0.406±0.079)比(0.221±0.064)mm2],调节性T细胞/CD4值降低[(9.06±0.50)%、(6.99±1.52)%比(12.30±2.06)%,均P<0.05]。粥样斑块面积与调节性T细胞/CD4值呈负相关(r=-0.739,P=0.001)。结论尼古丁可以促进动脉粥样硬化斑块的形成,可能与尼古丁减少调节性T细胞的数量相关。

Objective To investigate the effect of nicotine stimulation on atherosclerotic plaque formation and on pe ripheral blood Treg under the two different concentrations. Methods Eighteen 8-week-old ApoE knock-out male C57BL6J mice were randomly divided into three groups： @untreated control （intraperitoneal injection of 0. 1 mL/d saline）; （~）low-dose nicotine [intraperitoneal injection of 0.5 mg/（kg ~ d） nicotine dissolved in 0.1 mL saline]; @high-dose nicotine [intraperitoneal injection of 2.0 mg/（kg ~ d） nicotine dissolved in 0.1 mL saline] （all n= 6 ）. Flow cytometry was used to detect the changes in peripheral blood Treg. Aortic roots were dissected out for paraf- fin embedding and HE staining. Results After 12 weeks of treatment, compared to control group, the size of plaque area in low-dose nicotine and high-dose nicotine group increased significantly [（0. 304 ±0. 055）, （0. 406 ± 0.079） vs （0.221±0.064）mm2]; Treg/CD4 ratio decreased significantly [（9.06±0.50）%, （6.99±1.52）% vs （12.30±2.06）%, all P%0.05]. The size of plaque area was negatively correlated with the Treg/CD4 ratio （r= 0. 739, P=0. 001）. Conclusion Nicotine can induce atherosclerotic plaque formation, which can be due to the fact that nicotine reduced the number of Treg in peripheral blood.